Growth hormone promotes the reconstruction of injured axons in the hypothalamo-neurohypophyseal system

Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.

Vasopressin-induced hyponatremia in an adult normotensive trauma patient:A case report

BACKGROUND Arginine vasopressin is a neuropeptide produced in the hypothalamus and released by the posterior pituitary gland.In addition to maintaining plasma osmolarity,under hypovolemic or hypotensive conditions,it helps maintain plasma volume through renal water reabsorption and increases systemic vascular tone.Its synthetic analogues are widely used in the intensive care unit as a continuous infusion,in addition to hospital floors as an intravenous or intranasal dose.A limited number of cases of hyponatremia in patients with septic or hemorrhagic shock have been reported previously with vasopressin.We report for the first time a normotensive patient who developed vasopressin-induced hyponatremia.CASE SUMMARY A 39-year-old man fell off a forklift and sustained an axial load injury to his cranium.He had no history of previous trauma.Examination was normal except for motor and sensory deficits.The Imagine test showed endplate fracture at C7 and acute traumatic disc at C7 with cortical degeneration.He underwent cervical discectomy and fusion,laminectomy,and posterior instrumented fusion.After intensive care unit admission post-surgery,he developed hyponatremia of 121-124 mEq/L post phenylephrine and vasopressin infusion to maintain blood pressure maintenance.He was evaluated for syndrome of inappropriate secretion of antidiuretic hormone,hypothyroid,adrenal-induced,or diuretic-induced hyponatremia.At the end of extensive evaluation for the underlying cause of hyponatremia,vasopressin was discontinued.He was also put on fluid restriction,given exogenous desmopressin,and a dextrose 5%in water infusion to prevent osmotic demyelination syndrome caused by sodium overcorrection which improved his sodium level to 135 mmol/L.CONCLUSION The presentation of vasopressin-induced hyponatremia is uncommon in normotensive patients,and the most difficult aspect of this condition is determining the underlying cause of hyponatremia.Our case illustrates that,considering the vast differential diagnosis of hyponatremia in hospitalized patients,both hospitalists and intensivists should be aware of this serious complication of vasopressin therapy.

Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review

Septic shock treatment remains a major challenge for intensive care units,despite the recent prominent advances in both management and outcomes.Vasopressors serve as a cornerstone of septic shock therapy,but there is still controversy over the timing of administration.Specifically,it remains unclear whether vasopressors should be used early in the course of treatment.Here,we provide a systematic review of the literature on the timing of vasopressor administration.Research was systematically identified through PubMed,Embase and Cochrane searching according to PRISMA guidelines.Fourteen studies met the eligibility criteria and were included in the review.The pathophysiological basis for early vasopressor use was classified,with the exploration on indications for the early administration of mono-vasopressors or their combination with vasopressin or angiotensinII.We found that mortality was 28.1%-47.7%in the early vasopressors group,and 33.6%-54.5%in the control group.We also investigated the issue of vasopressor responsiveness.Furthermore,we acknowledged the subsequent challenge of administration of high-dose norepinephrine via peripheral veins with early vasopressor use.Based on the literature review,we propose a possible protocol for the early initiation of vasopressors in septic shock resuscitation.

血管升压素在肾脏和心血管活动调节中的作用

血管升压素(vasopressin,VP)是下丘脑内一些神经元合成和释放的一种九肽,具有很强的生物活性。VP一方面作为一种激素,由脑垂体后叶释放入血,参与对肾脏和心血管活动的调节;另一方面又作为中枢神经系统内的神经递质或调制物质,对参与心血管和肾脏活动调节的中枢内神经元的活动发生影响。 (一)VP神经元的分布 VP和催产素(oxytocin,OT)是最早从下丘脑组织中分离出的两种神经肽。VP神经元的细胞体主要分布在下丘脑的视(?)

SPECIFIC INHIBITION OF CONNEXIN 43 GENE EXPRESSION AFTER ACUPOINTS AND ACUPUNCTURE TREATMENT FOR PRIMARY DYSMENORRHEA

Objective To investigate the effect of acupuncture treatment on silencing the expression of Oonnexin 43 （Cx43）, and to study the analgesic mechanism of acupuncture treatment for primary dysmenorrhea （PD） in rats. Methods We used estrostilben to develop the model of primary dysmenorrhea in rat, and RNA interference technology to silence the expression of Cx43 in acupoints. Fifty female rats were randomly divided into five groups （n = 10 in each group） ： normal, model, acupuncture, acupuncture ＋ interference and acupuncture＋ interference control group, pSilencer-Cx43-shRNA and pSilencer-Oon-shRNA were injected locally into the acupoints in interference group and interference-control group, respectively. The incidence rate of writhe reaction over the period of 30 min was evaluated. The expression of the oxytocin receptor （OTR） and vasopressin receptor（VasR） in rat myometrium with Semiquantitative RT-POR and immunohistochemistry. Results （1）The mRNA and protein level of Cx43 in acupoints in interference group were significantly lower those of in the acupuncture group （P〈0.05）. There was no significant difference between acupuncture and interference-control group. （2） Acupuncture could significantly prolong the latency period of writhing body and decrease the number of writhing body as compared with that of model group and interference group. （3）The level of OTR and VasR mRNA and protein in the model group were significantly higher （P〈0.05） as compared to normal group. The results in acupuncture group and interference-control group were similar to the normal group. The results in interference group were similar to the model group. Conclusions Acupuncture may be useful in the treatment of the model of primary dysmenorrhea in the rats. Local injection of Cx43 shRNA expression vetor could silence the expression of Cx43 in acupoint and markedly influence acupuncture effect, demonstrating Cx43 is involved in acupuncture effect.

Is there an alternative therapy to cyanoacrylate injection for safe and effective obliteration of bleeding gastric varices?

TO THE EDITORWe read with interest the article entitled ＂Bleeding gastric varices： Results of endoscopic injection with cyanoacrylate at King Chulalongkorn Memorial Hospital＂ by Noophun et al. They performed n-butyl-2-cyanoacrylate （CA） injection therapy for bleeding gastric varices in twentyfour patients, and hemostasis was achieved in seventeen （71%） patients. They concluded that CA injection therapy was effective and safe for bleeding gastric varices. However, we disagreed with the author＇s conclusion.

Vasopressin in vasoplegic shock:A systematic review

BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is oftenresistant to conventional therapies for shock. Norepinephrine and epinephrine arestandards of care for vasoplegic shock, but vasopressin has increasingly been usedas a primary pressor in vasoplegic shock because of its unique pharmacology andlack of inotropic activity. It remains unclear whether vasopressin has distinctbenefits over standard of care for patients with vasoplegic shock.AIMTo summarize the available literature evaluating vasopressin vs non-vasopressinalternatives on the clinical and patient-centered outcomes of vasoplegic shock inadult intensive care unit (ICU) patients.METHODSThis was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegicshock after cardiac surgery. Randomized controlled trials, prospective cohorts,and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine,methylene blue, hydroxocobalamin, or other pressors were included. The primaryoutcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke,ICU length of stay, duration of vasopressor therapy, incidence of acute kidneyinjury stage II-III, and mechanical ventilation for greater than 48 h.RESULTSA total of 1161 studies were screened for inclusion with 3 meeting inclusioncriteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality,stroke, ventricular arrhythmias, and duration of mechanical ventilation weresimilar between groups. Conflicting results were observed for acute kidney injurystage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of staywith higher certainty of evidence in favor of vasopressin serving a protective rolefor these outcomes.CONCLUSIONVasopressin was not found to be superior to alternative pressor therapy for any ofthe included outcomes. Results are limited by mixed methodologies, small overallsample size, and heterogenous populations.

Hyponatremia in patients with heart failure

The present review analyses the mechanisms relating heart failure and hyponatremia,describes the association of hyponatremia with the progress of disease and morbidity/mortality in heart failure patients and presents treatment options focusing on the role of arginine vasopressin(AVP)-receptor antagonists.Hyponatremia is the most common electrolyte disorder in the clinical setting and in hospitalized patients.Patients with hyponatremia may have neurologic symptoms since low sodium concentration produces brain edema,but the rapid correction of hyponatremia is also associated with major neurologic complications.Patients with heart failure often develop hyponatremia owing to the activation of many neurohormonal systems leading to decrease of sodium levels.A large number of clinical studies have associated hyponatremia with increased morbidity and mortality in patients hospitalized for heart failure or outpatients with chronic heart failure.Treatment options for hyponatremia in heart failure,such as water restriction or the use of hypertonic saline with loop diuretics,have limited efficacy.AVP-receptor antagonists increase sodium levels effectively and their use seems promising in patients with hyponatremia.However,the effects of AVP-receptor antagonists on hard outcomes in patients with heart failure and hyponatremia have not been thoroughly examined.

Arginine vasopressin as a target in the treatment of acute heart failure

Congestive heart failure(CHF) is one of the most common reasons for hospitalization in the United States. Despite multiple different beneficial medications for the treatment of chronic CHF, there are no therapies with a demonstrated mortality benefit in the treatment of acute decompensated heart failure. In fact, studies of inotropes used in this setting have demonstrated more harm than good. Arginine vasopressin has been shown to be up regulated in CHF. When bound to the V1 a and/or V2 receptors, vasopressin causes vasoconstriction, left ventricular remodeling and free water reabsorption. Recently, two drugs have been approved for use that antagonize these receptors. Studies thus far have indicated that these medications, while effective at aquaresis(free water removal), are safe and not associated with increased morbidity such as renal failure and arrhythmias. Both conivaptan and tolvaptan have been approved for the treatment of euvolemic and hypervolemic hyponatremia. We review the results of these studies in patients with heart failure.

Hypothalamic paraventricular nucleus stimulation reduces intestinal injury in rats with ulcerative colitis

AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis(UC).METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the paraventricular nucleus(p VN), and the effect of the nucleus tractus solitarius(NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the p VN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin(IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the p VN in rats were detected by Western blot. Malondialdehyde(MDA) content and superoxide dismutase(SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulationof the p VN on rats with UC were eliminated after chemical damage to the p VN. After glutamate receptor antagonist kynurenic acid was injected into the p VN, the protective effects of the chemical stimulation of the p VN were eliminated in rats with UC. After AVpVl receptor antagonist([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of p VN on UC was also eliminated. After chemical stimulation of the p VN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic p VN provides a protective effect against UC injury in rats. Hypothalamic p VN, NTS and vagus nerve play key roles in this process.

Modulation of splanchnic circulation:Role in perioperativemanagement of liver transplant patients

Splanchnic circulation is the primary mechanism thatregulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods(e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure.

WJH 6^(th) Anniversary Special Issues(4): Cirrhosis Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin(AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2(vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phasetwo studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.

Expression of hippocampal corticosteroid receptors,as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus,in fornix transected rats

BACKGROUND： The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE： To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor （MR） and glucocorticoid receptor （GR） in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS： Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone （CRH） and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS： A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups （n = 45）. Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES： Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS： Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed （P 〈 0.05-0.01）. CONCLUSION： Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.

ARGININE VASOPRESSIN GENE EXPRESSION IN SUPRAOPTIC NUCLEUS AND PARAVENTRICULAR NUCLEUS OF HYPOTHALAMOUS FOLLOWING CEREBRAL ISCHEMIA AND REPERFUSION

Background. Our previous studies indicated that the increased arginine vasopressin(AVP) in ischemic brain regions of gerbils could exacerbate the ischemic brain edema. This experiments is further clarify the relation between AVP and cerebral ischemia at the molecular level. Methods. The contents of AVP, AVP mRNA, AVP immunoreactive(ir) neurons in supraoptic nucleus(SON) and paraventricular nucleus(PVN) after cerebral ischemia and reperfusion were respectively determined by radioimmunoassay(RIA), immunocytochemistry(ⅡC), situ hybridization and computed image pattern analysis. Results. The contents of AVP in SON, PVN were increased, and the AVP ir positive neurons in SON and PVN were also significantly increased as compared with the controls after ischemia and reperfusion. And there were very light staining of AVP ir positive neurons in the other brain areas such as suprachiasmatic nucleus (SC) and periventricular hypothalamic nucleus (PE), but these have no significant changes as compared with the controls. During different periods of cerebral ischemia (30～120 min) and reperfusion (30 min), AVP mRNA expression in SON and PVN were more markedly increased than the controls. Conclusions. The transcription of AVP gene elevated, then promoting synthesis and release of AVP in SON, PVN. Under the specific condition of cerebral ischemia and reperfusion, the activity and contents of central AVP increased abnormally is one of the important factors which causes ischemia brain damage.

The hemodynamic management of elderly patients with sepsis

Sepsis is among the most common reason for admission to intensive care units throughout the world. In the US and most Western nations sepsis is largely a disease of the elderly. Management of elderly patients with severe sepsis is challenging. Early recognition of this syndrome, together with the early administration of appropriate antibiotics and cautious fluid resuscitation is the cornerstone of therapy. Echocardiography together with non-invasive or invasive hemodynamic monitoring is recommended in patients who have responded poorly to fluids or have significant underlying cardiac disease. This paper reviews the hemodynamic changes that characterize sepsis, particularly as they apply to elderly patients and provides recommendations for the management of these patients.

Clinical trials comparing norepinephrine with vasopressin in patients with septic shock:A meta-analysis

Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I2 statistic, we used a fixed effects model(P≥0.1) and expressed the results as risk ratios(RRs) for dichotomous outcomes or as standardized mean differences(SMDs) for continuous data with 95% confidence intervals(CIs). Meta-analysis was conducted using Review Manager 5.1 software.Results: Seven trials(n=2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2%(840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin(RR 1.07; 95%CI 0.97-1.20; P=0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate(HR)(SMD 0.21; 95%CI-0.08-0.50; P=0.15), mean arterial pressure(MAP)(SMD 0.15; 95%CI-0.15-0.44; P=0.33), cardiac index(CI)(SMD-0.10; 95%CI-0.64-0.44; P=0.73), systemic vascular resistance index(SVRI)(SMD 0.15; 95%CI-0.39-0.70; P=0.58), oxygen delivery(DO2)(SMD-0.06; 95%CI-0.62-0.49; P=0.82), oxygen consumption(VO2)(SMD 0.03; 95%CI-0.52-0.59; P=0.91) or lactic acid(SMD 0.07; 95%CI-0.23-0.36; P=0.66). No significant heterogeneity was found in these comparisons(P≥0.1).Conclusions: There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.

Plasma L-ENK, AVP, ANP and serum gastrin in patients with syndrome of Liver-Qi-stagnation

AIM To investigate the pathophysiologic basis of syndrome of Liver Qi stagnation and parameters for clinical differentiation. METHODS Plasma L ENK, AVP, ANP and serum gastrin were determined by RIA in 84 patients with neurasthenia, mastodynia, chronic gastritis, and chronic cholecystitis presenting the same syndrome of Liver Qi stagnation in traditional Chinese medicine (TCM). Healthy subjects served as controls in comparison with patients having the same syndrome but with different diseases. RESULTS Among the patients with Liver Qi stagnation, the plasma L ENK, ANP and gastrin levels were 38 83ng/L ± 6 32ng/L , 104 11ng/L ± 29 01ng/L and 32 20ng/L ± 6 68ng/L , being significantly lower than those in the healthy controls ( t =3 34, 6 17, 4 48; P <0 01). The plasma AVP of the patient group ( 52 82ng/L ± 19 09ng/L ) was significantly higher than that of the healthy controls ( t =5 79, P <0 01). The above changes in patients having the same symptom complex but different diseases entities showed no significant differences, P >0 05. CONCLUSION The syndrome of Liver Qi stagnation is closely related to the emotional modulatory abnormality of the brain, with decrease of plasma L ENK, ANP and gastrin, and increase of plasma AVP as the important pathophysiologic basis.

Vasopressin decreases neuronal apoptosis during cardiopulmonary resuscitation

The American Heart Association and the European Resuscitation Council recently recommend- ed that vasopressin can be used for cardiopulmonary resuscitation, instead of epinephrine. However, the guidelines do not discuss the effects of vasopressin during cerebral resuscitation. In this study, we intraperitoneally injected epinephrine and/or vasopressin during cardiopul- monary resuscitation in a rat model of asphyxial cardiac arrest. The results demonstrated that, compared with epinephrine alone, the pathological damage to nerve cells was lessened, and the levels of c-Iun N-terminal kinase and p38 expression were significantly decreased in the hippo- campus after treatment with vasopressin alone or the vasopressin and epinephrine combination. No significant difference in resuscitation effects was detected between vasopressin alone and the vasopressin and epinephrine combination. These results suggest that vasopressin alone or the vasopressin and epinephrine combination suppress the activation of mitogen-activated protein kinase and c-Iun N-terminal kinase signaling pathways and reduce neuronal apoptosis during cardiopulmonary resuscitation.

Modeling cardiac arrest and resuscitation in the domestic pig

Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca2+ overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation(CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.

Aquaporin-4 in the formation of cerebral edema following severe burns What role do arginine vasopressin levels play?

BACKGROUND： Aquaporin-4 （AQP-4）, which is able to rapidly transport water within the brain, is highly expressed in brain tissue. It also plays an important role in the formation of cerebral edema following brain injury. However, the role of AQP-4 in the formation of cerebral edema following severe bums remains unknown. OBJECTIVE： To study changes in AQP-4 protein and mRNA expression during formation of cerebral edema following severe burns, and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin （AVP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Research Center of Neuroscience, Chongqing Medical University from 2007 to 2008. MATERIALS： Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology, China; in situ hybridization kit was provided by Wuhan Boster Biotechnology, China; rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon, USA; AVP radioimmunoassay kit was provided by the Research Department of Neurobiology, the Second Military Medical University of Shanghai, China. METHODS： A total of 180 adult, healthy, Wistar rats were randomly assigned to control and burn groups with 30 rats in each group. The burn group was observed at five different time points： 2, 6, 12, 24, and 48 hours after burn. Hair on the mouse back was removed to expose skin on the back. After 1 day, skin with the hair removed was dipped into 100℃ water for 15 seconds to induce grade III bum injury that measures 30% of total bum surface area. MAIN OUTCOME MEASURES： Brain water content was measured using the dry-wet weight method. AQP-4 protein and mRNA expressions were detected using immunohistochemistry, in situ hybridization, Western blot, and reverse transcription-polymerase chain reaction; dynamic changes in plasma AVP were detected using radioimmunoassay. RESULTS： Brain water content gradually increased following severe burn injury. AQP-4 protein and mRNA expressions were upregulated in the supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, hippocampus, choroid plexus, and cerebral cortex. Plasma AVP levels increased following burn injury. AQP-4 protein and mRNA expressions positively correlated with brain water content and AVP levels during formation of cerebral edema （r= 0.870, 0.848, P 〈 0.01）. CONCLUSION： AQP-4 participated in the formation of cerebral edema following burn injury. Plasma AVP upregulated AQP-4 expression in brain tissue, thereby promoting formation of cerebral edema.